The overall goal of this proposal is to facilitate the development of Dr. Aimee Zaas into an independent investigator in the genetic basis of host-pathogen interaction. Dr. Zaas proposes a structured five-year career development plan, with rigorous research training under the mentorship of Drs. David Schwartz and John Perfect. As an integral part of career development, Dr. Zaas will also pursue formal training in genetics, genomics, and statistical analysis. This training will culminate in a Master's of Health Sciences in Genomics degree. At the conclusion of this award, Dr. Zaas will have gained considerable skills in murine models of fungal infection, identification of the genetic basis of complex traits using computerized murine single nucleotide polymorphism databases and positional cloning, as well as validation of animal model findings in human cohorts. This knowledge can be applied to future investigations of the genetic basis of fungal infection, as well as be used to direct antifungal prophylaxis in high-risk patients. The research plan involves elucidating the genetic basis of susceptibility to the fungal pathogen Aspergillus fumigatus. The genetic basis of host susceptibility to invasive aspergillosis (IA) is poorly understood. Murine models of IA can be used for gene discovery through the availability of murine single nucleotide polymorphism databases and through positional candidate gene discovery. Using robust phenotypic differences between inbred strains of mice in response to A. fumigatus infection, this proposal will identify and characterize genetic polymorphisms related to IA susceptibility in mice and validate these findings in a cohort of human bone marrow transplant donors and recipients.